Answer: A

Pityriasis lichenoides et varioliformis acuta (PLEVA) is the acute form of pityriasis lichenoides (PL), a rare cutaneous inflammatory condition of unknown etiology.1 PLEVA, also known as Mucha-Habermann disease, was first characterized by the Austrian dermatologist Viktor Mucha in 1916 and the German dermatologist Rudolf Habermann in 1925.2

PLEVA falls along the continuum of PL conditions that range from the milder pityriasis lichenoides chronica (PLC) to the life-threatening febrile ulceronecrotic Mucha-Habermann disease (FUMHD).1,2 Collectively, these conditions pose a series of diagnostic and managerial challenges for patients and clinicians.3

PLEVA has no clearly defined incidence, prevalence, risk factors, or racial or geographic distribution. It occurs most frequently in children and young adults (aged 10 to 30 years), with a slight predisposition in men.1,2

The etiology and pathogenesis of PLEVA are not well understood. It generally is described as a lymphoproliferative disorder, with 2 prevailing theories classifying it as either a premalignant T-cell dyscrasia or a reactive immune response to infection.3 The former is based on identification of clonal T-cell populations in patients with PLEVA and FUMHD, as well as rare reports of cutaneous T-cell lymphoma following PLEVA and PLC.4,5

The aberrant immune response theory stems from reports of PLEVA arising in the aftermath of infections caused by bacteria (Staphylococcus aureus, Streptococcus pyogenes), viruses (Epstein-Barr virus, parvovirus B19 [fifth disease], hepatitis B virus, adenovirus), or parasites (Toxoplasma gondii). PLEVA even has been described as an early cutaneous manifestation of HIV infection.6 It has been classified as an immune complex-mediated hypersensitivity vasculitis.3

PLEVA presents clinically as a subacute-to-acute eruption of multiple erythematous macules, most prominently along the anterior trunk, flexural surfaces, and proximal extremities. The macules evolve into vesiculopustules, with hemorrhaging, necrosis, ulceration, and crusting.1-4 These scaly, red-brown papules have an appearance that is more consistent with PLC.2

A characteristic sign of PLEVA is the presence of lesions at multiple stages of development.1,2 As individual lesions resolve over the course of a few weeks, new lesions develop due to ongoing disease.1,2 The lesions usually are asymptomatic but can be associated with pruritus or burning.1-3

PLEVA typically is a benign, self-limited disease. Following the resolution of lesions, there may be some hypopigmentation or hyperpigmentation.3 There is little mucosal involvement, and systemic symptoms normally are absent.1 General PLEVA resolves faster than localized PLEVA.2 Occasionally, patients with PLEVA patients will completely transition to PLC.3

Histologically, PLEVA presents as a constellation of features, none of which are pathognomonic. These include:1,2

  • Parakeratosis, spongiosis, dyskeratosis, acantholysis, vacuolization of the basal layer, and focal epidermal necrolysis;
  • A moderately dense, wedge-shaped lymphohistiocytic perivascular inflammatory infiltrate, extending from the papillary to the reticular dermis and obscuring the dermoepidermal junction; and
  • Dilation/engorgement of blood vessels, vascular congestion, dermal hemorrhage, and extravasation of lymphocytes and erythrocytes into the epidermis.

Immunohistochemical staining (hematoxylin and eosin [H&E]) of the inflammatory infiltrate reveals a predominance of CD8+ cytotoxic T lymphocytes.7 There are no specific serologic tests for PLEVA, although some tests can be used to uncover a preceding or coexisting infection.1

Compared with PLEVA, FUMHD is associated with clinical symptoms that are more severe.1-3 It can arise de novo or from preexisting PLEVA, with rapid progression to severe ulceronecrotic disease, painful hemorrhagic bullae, mucosal involvement, and high fevers.2 Systemic manifestations include cardiomyopathy, interstitial pneumonitis, malabsorption, abdominal pain, central nervous system vasculitis, and sepsis due to secondary infection of bullae and pustules.1,2 Resolution of skin lesions results in atrophic scarring.1-3

FUMHD has a poor prognosis (25% mortality rate) and is, thus, considered a dermatologic emergency.2,3 The histologic features of FUMHD are similar to those of PLEVA, with leukocytoclastic vasculitis, denser perivascular infiltrates, and more widespread necrosis.3 Serology commonly shows elevations in erythrocyte sedimentation rate or C-reactive protein levels.1,3

The differential diagnosis for PLEVA is extensive due to its intermediate position in the PL spectrum and its shared clinical features with multiple inflammatory conditions.1,2 Lymphomatoid papulosis (LyP) most closely resembles PLEVA, with eruption of inflammatory papules and small nodules regressing over a few weeks.1,2 Histologically, LyP shows little basal layer vacuolization and is characterized by a dense infiltrate of CD30+ (not CD8+) T lymphocytes.1,8 PLC presents as gradually developing red-brown maculopapules with overlying micaceous (silvery) scale scattered across the trunk and proximal extremities.

Other conditions that mimic PLEVA include varicella (shorter disease course), disseminated herpes simplex, Gianotti Crosti syndrome (lymphadenopathy and hepatomegaly seen), Langerhans cell histiocytosis rash (localized to seborrheic or intertriginous areas), and multiple arthropod bites (vesiculation and necrosis infrequent).1-3 When cutaneous findings raise the suspicion for PLEVA, biopsy is required to confirm this diagnosis and rule out other conditions.1-3

Since PLEVA is benign and typically self-limited, it is possible for a patient to be followed in clinic without treatment if the disease is limited, nonscarring, and asymptomatic. However, patients with extensive, persistent, scarring, or symptomatic PLEVA can be treated with systemic antibiotics, phototherapy, topical agents, and systemic immunomodulators.9 Examples of these treatments include the following:9

  • Antibiotics: doxycycline and minocycline (adults) and erythromycin (children) are used for their anti-inflammatory and immune-response properties.
  • Ultraviolet (UV) light treatments: UVB is a first-choice therapy, followed by psoralen plus UVA and broadband/narrowband UVB phototherapy.
  • Topical corticosteroids and antihistamines can be used to manage pruritic symptoms but do not alter the disease course.
  • For severe refractory PLEVA and FUMHD, methotrexate has been found to be the most efficacious therapy.

Other treatments used for FUMHD have included acyclovir, dapsone, cyclosporine, and intravenous immunoglobulin (IVIG). There also is a report showing that infliximab therapy may be beneficial for FUMHD, given the elevated tumor necrosis factor-α levels seen in patients with FUMHD.10

Due to clinical suspicion for PLEVA, the patient in this case underwent a 4-mm punch biopsy of his largest lesion. Because of his recent infection, he also was tested for Group A Streptococcus and Epstein-Barr viral infections. The histologic results of the biopsy supported the diagnosis of PLEVA, although serology testing was negative. The patient was prescribed a topical corticosteroid for symptomatic relief and told to follow up in 3 months. At his follow-up visit, most of his lesions had cleared and there was no evidence of scarring.

Click to the next page for Case 2.